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Results of the phase 1/2 basket clinical trial showed an overall response rate of 31% and a 6-month clinical benefit of 48%. In patients with hepatic metastases, who generally have a poor prognosis, the clinical benefit was 48% as well.

"The benefit was durable, with an estimated median duration of response of 7.4 months and an estimated median progression-free survival of 6.8 months," said lead investigator Aditya Bardia, MD, MPH, Massachusetts General Hospital Cancer Center, Boston, who presented the results. "The side effects were also predictable and manageable. There were only 2 patients who discontinued treatment because of adverse events," Dr Bardia added.

HR-positive, HER2-negative metastatic breast cancer is the most common form of metastatic breast cancer in the United States, said Dr Bardia. Although patients with HR-positive breast cancer typically receive endocrine-based therapies in the front-line setting and subsequently chemotherapy, the response rates to late-in-life therapies are low. In particular, said Dr Bardia, patients with visceral metastases have a poor prognosis.

Sacituzumab govitecan

Sacituzumab govitecan is a first-in-class antibody-drug conjugate that provides sustained delivery and rapid release of anticancer agents directly to the tumor while sparing healthy ­surrounding tissues.

Investigators evaluated sacituzumab govitecan in a phase 1/2 basket trial that included patients with metastatic solid tumors that progressed with ≥1 standard therapeutic regimens for the disease.

The study included patients with breast cancer, epithelial cancer, lung cancer, and other types of cancer. In­terim data from the HR-positive, HER2-negative breast cancer cohort were presented at ASCO 2018.

Durable Responses

Between February 2015 and June 2017, Dr Bardia and colleagues enrolled 54 patients with HR-positive, HER2-­negative metastatic breast cancer. Of these patients, 98% had received ≥1 lines of chemotherapy for metastatic disease, and 100% had received hormonal therapy for their HR-positive metastatic breast cancer.

"This was a heavily pretreated patient population," said Dr Bardia, noting that 82% of patients had liver metastases. "The median number of prior metastatic treatment lines was 5, the median number of metastatic hormone therapy lines was 3, and the median number of prior metastatic chemotherapy lines was 2."

Nevertheless, treatment was generally well-tolerated, with no treatment-related deaths. Although 42% of patients had grade 3 or 4 neutropenia, the incidence of severe diarrhea was only 4%. Other side effects included fatigue, alopecia, as well as decreased appetite, but no peripheral neuropathy was seen in this study. Adverse events were managed with supportive medications or dose modifications, and only 2 patients discontinued treatment because of adverse events, according to the researchers.

"The responses were durable and usually occurred early. However, there were some patients who had late responses," said Dr Bardia, adding that the median duration of response was 7.4 months, and the median time to onset of response was 2.3 months.

In addition, responses occurred in patients who previously received cyclin-dependent kinase (CDK)4/CDK6 inhibitors, as well as in those who had not received such previous treatment. Although the progression-free survival was 6.8 months, the data are not ­completely mature, said Dr Bardia. He reported that 7 patients are still continuing treatment with sacituzumab ­govitecan, as of the last assessment.

Finally, a subgroup analysis of sacituzumab govitecan showed no significant difference based on age, onset of metastatic disease, number of previous lines of chemotherapy for metastatic disease, previous hormone therapy for metastatic disease, or use of CDK4/CDK6 inhibitors. In patients with liver involvement, the response rate was 27% and the clinical benefit rate was 48%.

Additional studies that include rational combinations are being evaluated for metastatic breast cancer and other metastatic solid tumors, Dr Bardia ­concluded.